Technology of deep brain stimulation: current status and future directions

Abstract

Deep brain stimulation (DBS) is a neurosurgical procedure that allows targeted circuit-based neuromodulation. DBS is a standard of care in Parkinson disease, essential tremor and dystonia, and is also under active investigation for other conditions linked to pathological circuitry, including major depressive disorder and Alzheimer disease. Modern DBS systems, borrowed from the cardiac field, consist of an intracranial electrode, an extension wire and a pulse generator, and have evolved slowly over the past two decades. Advances in engineering and imaging along with an improved understanding of brain disorders are poised to reshape how DBS is viewed and delivered to patients. Breakthroughs in electrode and battery designs, stimulation paradigms, closed-loop and on-demand stimulation, and sensing technologies are expected to enhance the efficacy and tolerability of DBS. In this Review, we provide a comprehensive overview of the technical development of DBS, from its origins to its future. Understanding the evolution of DBS technology helps put the currently available systems in perspective and allows us to predict the next major technological advances and hurdles in the field.

Fig. 1. Timeline of technology development for DBS.

DBS, deep brain stimulation; IPG, implantable pulse generator.

Fig. 2. DBS electrode configurations.

a | Common electrode configurations for deep brain stimulation (DBS). Dark grey regions illustrate electrode contacts, which can be activated to deliver current. Electrode designs vary with regard to the spacing between contacts as well as the number and shape of contacts. Greater contact spacing expands the range of neural targets, whereas smaller contact spacing facilitates more precise stimulation control. b | Modes of stimulation, depending on the type of DBS system in use. Unipolar stimulation refers to current being directed from the battery to the contact or vice versa. Bipolar stimulation indicates current flowing between electrode contacts, with at least one functioning as an anode and one as a cathode. Interleaving stimulation refers to the alternation of different stimulation settings. Multiple level stimulation enables multiple neural targets to be stimulated, provided that they lie along the electrode trajectory. With directional stimulation, current can be directed or ‘shaped’ on the basis of local anatomy or clinical symptoms.

Fig. 3. Stimulation waveform shapes and temporal stimulation patterns.

In deep brain stimulation (DBS), waveform shapes are repeated at interpulse intervals to create a stimulation pattern. a | Conventional asymmetric biphasic DBS waveform with a short-duration cathodic phase followed by an interphase delay and a long-duration anodic (recharge) phase. b | Symmetric biphasic DBS waveform with equal-duration cathodic and anodic phases. c | Symmetric biphasic DBS waveform with zero interphase delay. d | Reversal of the standard pulse phase order of a symmetric biphasic DBS waveform. e | Regular temporal pattern of stimulation with fixed interpulse intervals (typically ~7.7 ms or ~130 Hz). f | Non-regular temporal pattern of stimulation with random interpulse intervals. g | Burst pattern of stimulation with several pulses at short interpulse intervals followed by a long interpulse interval. h | Stimulation pattern for coordinated reset with bursts of stimulation distributed across four different electrode contacts, with each row corresponding to the stimulation pattern delivered to each electrode contact.

Fig. 4. Adaptive DBS in Parkinson disease.

a | Stimulating and recording from the deep brain stimulation (DBS) electrode. When the patient is in the off-levodopa phase, which is characterized by slow movements and muscle stiffness, the local field potential activity at the electrode contacts contains prominent oscillations at ~20 Hz (beta activity). The amplitude of these oscillations varies over time and high-frequency DBS is delivered whenever an amplitude threshold is crossed. An alternative approach is to deliver DBS with an intensity that is proportional to the beta amplitude. b | Stimulating DBS electrode and recording from an electrocorticographic (ECOG) electrode strip overlying the motor cortex. When the patient is on levodopa and dyskinetic, the ECOG activity picked up by the strip electrode contains prominent oscillations at ~70 Hz (gamma activity). The amplitude of these oscillations is monitored and DBS is stopped or reduced when an amplitude threshold is crossed. STN, subthalamic nucleus.

Fig. 5. DBS neuroimaging.

a | Postoperative neck and chest X-rays showing an implanted deep brain stimulation (DBS) system with electrodes and extension wires (left image) and the implantable pulse generator implanted over the chest area (right image) b | Novel MRI visualization techniques, including quantitative susceptibility mapping (QSM) and fast grey matter acquisition T1 inversion recovery, have improved the visualization of subcortical structures. QSM coronal slice shows the subthalamic nucleus (outlined) — the most commonly targeted structure in Parkinson disease. c | Ultra-high-field preoperative MRI is increasingly used in surgical planning and research. T1-weighted axial slice intrathalamic nuclei (labelled in the right-hand image). d | On the basis of MRI metallic artefacts associated with DBS electrodes (shown on T2-weighted coronal image and axial image (arrowheads) on the left), the electrodes can be localized and reconstructed in 3D using specialized software. CT scans can also be used for electrode localization. DBS settings, including active contact, voltage, pulse width and impedance, can be used to estimate the electric field (white arrows, right image) surrounding the DBS electrodes. Heuristic assumptions or axonal cable models can be used to estimate the volume of tissue activated (VTA, red, right image). e | The VTA can be used in connectivity analyses informed by metrics such as resting-state functional MRI (top left) and diffusion-weighted, imaging-based tractography (bottom left) to determine the effects of DBS on distributed brain regions. CeM, central medial nucleus; CM, centromedian nucleus; IC, internal capsule; MD, mediodorsal nucleus; MTT, mammillothalamic tract; PuM, medial pulvinar nucleus; PuL, lateral pulvinar nucleus; VA, ventral anterior nucleus; VLA, ventral lateral anterior nucleus; VLP, ventral lateral posterior nucleus; VPL, ventral posterolateral nucleus. Part a is adapted with permission from REF., Boutet, A. et al. Radiology (2019) 293, 174–183, Radiological Society of North America. Part b is adapted with permission from REF., Liu, T. et al. Radiology (2013) 269, 216–223, Radiological Society of North America. Part c is adapted with permission from REF., Elsevier. Part e is adapted with permission from REF., Wiley.

Fig. 6. Future visions for DBS.

a | A typical currently available deep brain stimulation (DBS) configuration b | A predicted future DBS configuration.